Project Summary Periodontal disease is a chronic inflammatory process in the periodontal tissue. It occurs in approximately 48% of the U.S. adult population and is the leading cause of tooth loss among adults. Guided tissue generation (GTR) is a widely-used, well-documented and clinically predictable technique to treat periodontal disease and dental/craniofacial defects by placing a polymeric membrane between epithelial tissue and periodontal ligament/bone tissue. This membrane serves as a barrier to protect the slower-growing periodontal ligament and bone tissues from the invasion of faster-growing epithelial tissue, but it should also allow exchange of fluids and signals between different tissues. A number of barrier membranes have been developed over the past decades, but current products are very costly and have limitations. Avian eggshell membrane is a semi-permeable fibrous membrane between egg-white and eggshell. It is available in abundant quantities as a waste product from the poultry and food industry. Natural eggshell membrane is composed of a highly-crosslinked interwoven protein fiber network with a unique double-layered structure. It not only allows excellent water/oxygen exchange and satisfies the need of embryo development, but also serves as a natural barrier membrane against the invasion of microorganisms and other challenges from the external environment. Inspired by the similarity of eggshell membrane and GTR membrane as a barrier membrane, we propose this project to explore the feasibility of developing an innovative and biomimetic artificial eggshell membrane for GTR application using a reactive electrospinning technique and response surface methodology (RSM), which can simulate the unique composition and microstructure of natural eggshell membrane. Our new membrane is a multiple-component system which contains soluble eggshell membrane protein (SEP), mechanically stable poly (lactic-co-glycolic acid) (PLGA) and osseoinductive nano-hydroxyapatite particles (nanoHAp). It also possesses a bio- inspired double-layered structure, which includes an outer barrier PLGA layer (adjacent to the gingival tissue) and an inner bioactive SEP/PLGA/nano-HAp layer (adjacent to the periodontal/bone tissue). The long-term goal of our proposed project is to improve the clinical outcome of the GTR technique by using this biomimetic membrane, as well as lay a foundation for converting eggshell membrane derived materials from an abundant industrial by-product to a new, green and promising biomaterial for dentistry and medicine.